The Dual Effect Of Membrane Potential On Sodium Conductance In The Giant Axon Of Loligo
497
J. Physiol. (1952) ii6, 497-506
THE DUAL EFFECT OF MEMBRANE POTENTIAL ON SODIUM CONDUCTANCE IN THE GIANT AXON OF LOLIGO
BY A. L. HODGKIN AND A. F. HUXLEY From the Laboratory of the Marine Biological Association, Plymouth, and the Physiological Laboratory, University of Cambridge
(Received 24 October 1951) This paper contains a further account of the electrical properties of the giant axon of Loligo. It deals with the 'inactivation' process which gradually reduces sodium permeability after it has undergone the initial rise associated with depolarization. Experiments described previously (Hodgkin & Huxley, 1952a, b) show that the sodium conductance always declines from its initial maximum, but they leave a number of important points unresolved. Thus they give no information about the rate at which repolarization restores the ability of the membrane to respond with its characteristic increase of sodium conductance. Nor do they provide much quantitative evidence about the influence of membrane potential on the process responsible for inactivation. These are the main problems with which this paper is concerned. The experimental method needs no special description, since it was essentially the same as that used previously (Hodgkin, Huiley & Katz, 1952; Hodgkin & Huxley, 1952b). RESULTS
The influence of a small change in membrane potential on the ability of the membrane to undergo its increase in sodium permeability is illustrated by Fig. 1. In this experiment the membrane potential was changed in two steps. The amplitude of the first step was -8 mV. and its duration varied between O and 50 msec. This step will be called the conditioning voltage (V1). It was followed by a second step called the test voltage (V2) which was kept at a constant amplitude of -44 mV. Record A gives the current observed with the test voltage alone. B-F show the effect of preceding this by a conditioning pulse of varying duration. Although the depolarization of 8 mV. was not associated with any appreciable inward current it greatly altered the subsequent response of the nerve. Thus, if the conditioning voltage lasted longer than 20 msec., it reduced the inward
498 A. L. HODGKIN AND A. F. HUXLEY current during the test pulse by about 40%. At intermediate durations the inward current decreased along a smooth exponential curve with a time constant of about 7 msec. The outward current, on the other hand, evidently behaved in a different manner; for it may be seen to approach a final level which was independent of the duration of the conditioning step. This is. consistent with the observation that depolarization is associated with a maintained increase in potassium conductance (Hodgkin & Huxley, 1952a). Membrane current
Membrane potential
0
AC
-44 -
44 -44
-44 E
0.
3040.50.0 10 20 30 40F5
msec. msec. Fig. 1. Development of 'inactivation' during constant depolarization of 8 mV. Left-hand column: time course of membrane potential (the numbers show the displacement of the membrane potential from its resting value in mV.). Right-hand column: time course of membrane current density. Inward current is shown as an upward deflexion. (The vertical lines show the 'sodium current' expected in the absence of a conditioning step; they vary between 1-03 mA./cm.' in A and 0-87 mA./om.' in G). Axon 38; compensated feed-back; temperature 50 C.
Fig. 2 illustrates the converse process of raising the membrane potential before applying the test pulse. In this case the conditioning voltage improved the state of the nerve for the inward current increased by about 70 % if thefirst step lasted longer than 15 msec. This finding is not altogether surprising, for the resting potential of isolated squid axons is less than that of other excitable cells (Hodgkin, 1951) and is probably lower than that in the living animal. A convenient way of expressing these results is to plot the amplitude of the sodium current during the test pulse against the duration of the conditioning
MEMBRANE POTENTIAL AND SODIUM CONDUCTANCE 499 pulse. For this purpose we used the simple method of measurement illustrated by Fig. 3 (inset). This procedure avoids the error introduced by variations of potassium conductance during the first step and should give reasonable results for V > -15 mV. With larger depolarizations both the method of measurement and the interpretation of the results become somewhat doubtful, since there may be appreciable sodium current during the conditioning period. Two Membrane potential
Membrane current
Al
-2
-44
A
C
-44
DF>
J. Physiol. (1952) ii6, 497-506
THE DUAL EFFECT OF MEMBRANE POTENTIAL ON SODIUM CONDUCTANCE IN THE GIANT AXON OF LOLIGO
BY A. L. HODGKIN AND A. F. HUXLEY From the Laboratory of the Marine Biological Association, Plymouth, and the Physiological Laboratory, University of Cambridge
(Received 24 October 1951) This paper contains a further account of the electrical properties of the giant axon of Loligo. It deals with the 'inactivation' process which gradually reduces sodium permeability after it has undergone the initial rise associated with depolarization. Experiments described previously (Hodgkin & Huxley, 1952a, b) show that the sodium conductance always declines from its initial maximum, but they leave a number of important points unresolved. Thus they give no information about the rate at which repolarization restores the ability of the membrane to respond with its characteristic increase of sodium conductance. Nor do they provide much quantitative evidence about the influence of membrane potential on the process responsible for inactivation. These are the main problems with which this paper is concerned. The experimental method needs no special description, since it was essentially the same as that used previously (Hodgkin, Huiley & Katz, 1952; Hodgkin & Huxley, 1952b). RESULTS
The influence of a small change in membrane potential on the ability of the membrane to undergo its increase in sodium permeability is illustrated by Fig. 1. In this experiment the membrane potential was changed in two steps. The amplitude of the first step was -8 mV. and its duration varied between O and 50 msec. This step will be called the conditioning voltage (V1). It was followed by a second step called the test voltage (V2) which was kept at a constant amplitude of -44 mV. Record A gives the current observed with the test voltage alone. B-F show the effect of preceding this by a conditioning pulse of varying duration. Although the depolarization of 8 mV. was not associated with any appreciable inward current it greatly altered the subsequent response of the nerve. Thus, if the conditioning voltage lasted longer than 20 msec., it reduced the inward
498 A. L. HODGKIN AND A. F. HUXLEY current during the test pulse by about 40%. At intermediate durations the inward current decreased along a smooth exponential curve with a time constant of about 7 msec. The outward current, on the other hand, evidently behaved in a different manner; for it may be seen to approach a final level which was independent of the duration of the conditioning step. This is. consistent with the observation that depolarization is associated with a maintained increase in potassium conductance (Hodgkin & Huxley, 1952a). Membrane current
Membrane potential
0
AC
-44 -
44 -44
-44 E
0.
3040.50.0 10 20 30 40F5
msec. msec. Fig. 1. Development of 'inactivation' during constant depolarization of 8 mV. Left-hand column: time course of membrane potential (the numbers show the displacement of the membrane potential from its resting value in mV.). Right-hand column: time course of membrane current density. Inward current is shown as an upward deflexion. (The vertical lines show the 'sodium current' expected in the absence of a conditioning step; they vary between 1-03 mA./cm.' in A and 0-87 mA./om.' in G). Axon 38; compensated feed-back; temperature 50 C.
Fig. 2 illustrates the converse process of raising the membrane potential before applying the test pulse. In this case the conditioning voltage improved the state of the nerve for the inward current increased by about 70 % if thefirst step lasted longer than 15 msec. This finding is not altogether surprising, for the resting potential of isolated squid axons is less than that of other excitable cells (Hodgkin, 1951) and is probably lower than that in the living animal. A convenient way of expressing these results is to plot the amplitude of the sodium current during the test pulse against the duration of the conditioning
MEMBRANE POTENTIAL AND SODIUM CONDUCTANCE 499 pulse. For this purpose we used the simple method of measurement illustrated by Fig. 3 (inset). This procedure avoids the error introduced by variations of potassium conductance during the first step and should give reasonable results for V > -15 mV. With larger depolarizations both the method of measurement and the interpretation of the results become somewhat doubtful, since there may be appreciable sodium current during the conditioning period. Two Membrane potential
Membrane current
Al
-2
-44
A
C
-44
DF>
